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Context.— The prostate sampling methods for radical cystoprostatectomy (RCP) specimens may affect pathologic results. Objective.— To investigate the impact on the tumor stage and clinicopathologic features according to the prostate sampling method for RCP specimens. Design.— From 2016 to 2017, the prostate in RCP was minimally and conventionally embedded (group 1, n = 98). From 2017 to 2018, it was completely embedded (group 2, n = 102). Results.— Group 2 was more likely to have prostatic ducts or acini involvement by urothelial carcinoma in situ component (27% versus 10%, P = .002) and prostate involvement (30% versus 13%, P = .003) than group 1. Although there were cases with prostatic stromal invasion in group 2 (14% versus 7%, P = .13), it was not statistically significant. In all, 6 cases were upstaged by subepithelial prostatic stromal invasion through intraurethral extension according to the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. Tumor location and the presence of concurrent carcinoma in situ were strongly associated with prostate involvement of urothelial carcinoma. Prostatic adenocarcinoma (PA) was incidentally identified in 47 cases (23.5%). Incidental PA and clinically significant PA were more often identified in group 2 than group 1 (38% versus 8%, P < .01 and 15% versus 6%, P = .048, respectively). Conclusions.— A complete prostate examination in RCP specimens can be suggested, since the final pathologic stage can be changed through a thorough prostate examination especially in accord with the AJCC staging manual 8th edition. In addition, the complete prostate analysis could detect more incidental and clinically significant PA.

Background Chemotherapy-induced cardiotoxicity is a well-recognized adverse effect of chemotherapy. Quantitative T1-mapping cardiovascular magnetic resonance (CMR) is useful for detecting subclinical myocardial changes in anthracycline-induced cardiotoxicity. The aim of the present study was to histopathologically validate the T1 and T2 mapping parameters for the evaluation of diffuse myocardial changes in rat models of cardiotoxicity. Methods Rat models of cardiotoxicity were generated by injecting rats with doxorubicin (1 mg/kg, twice a week). CMR was performed with a 9.4 T ultrahigh-field scanner using cine, pre-T1, post-T1 and T2 mapping sequences to evaluate the left ventricular ejection fraction (LVEF), native T1, T2, and extracellular volume fraction (ECV). Histopathological examinations were performed and the association of histopathological changes with CMR parameters was assessed. Results Five control rats and 36 doxorubicin-treated rats were included and classified into treatment periods. In the doxorubicin-treated rats, the LVEF significantly decreased after 12 weeks of treatment (control vs. 12-week treated: 73 ± 4% vs. 59 ± 9%, P = 0.01). Increased native T1 and ECV were observed after 6 weeks of treatment (control vs. 6-week treated: 1148 ± 58 ms, 14.3 ± 1% vs. 1320 ± 56 ms, 20.3 ± 3%; P = 0.005, P P = 0.03, 0.03, 0.02, respectively). In the univariable analysis, vacuolar change showed the highest correlation with native T1 value (R = 0.60, P P P = 0.01), and vacuolar change and fibrosis were significant factors for change in ECV (P = 0.006, P Conclusions Quantitative T1 and T2 mapping CMR is a useful non-invasive tool reflecting subclinical histopathological changes in anthracycline-induced cardiotoxicity.

Background Urothelial carcinoma (UC) accounts for roughly 90% of bladder cancer, and has a high propensity for diverse differentiation. Recently, certain histologic variants of UC have been recognized to be associated with unfavorable clinical outcomes. Several UC studies have also suggested that tumor budding is a poor prognostic marker. Distant metastasis of UC after radical cystectomy is not uncommon. However, these metastatic lesions are not routinely confirmed with histology. Methods We investigated the histopathologic features of 13 cases of UC with biopsy-proven distant metastases, with a special emphasis on histologic variants and tumor budding. Results Lymph nodes (6/13, 46%) were the most common metastatic sites, followed by the lung (4/13, 31%), liver (4/13, 31%), and the adrenal gland (2/13, 15%). The histologic variants including squamous (n=1), micropapillary (n=4), and plasmacytoid (n=1) variants in five cases of UC. Most histologic variants (4/5, 80%) of primary UCs appeared in the metastatic lesions. In contrast, high-grade tumor budding was detected in six cases (46%), including one case of non-muscle invasive UC. Our study demonstrates that histologic variants are not uncommonly detected in distant metastatic UCs. Most histologic variants seen in primary UCs persist in the distant metastatic lesions. In addition, high-grade tumor budding, which occurs frequently in primary tumors, may contribute to the development of distant metastasis. Conclusions Therefore, assessing the presence or absence of histologic variants and tumor budding in UCs of the urinary bladder, even in non-muscle invasive UCs, may be useful to predict distant metastasis.

Antecedentes: La remisión espontánea (RE) del cáncer es un fenómeno muy raro, cuyo mecanismo se desconoce. En particular, hay escasos reportes de RE de cáncer de pulmón no-microcítico (CPNM). Presentamos el caso de una mujer de 74 años con CPNM avanzado, poco diferenciado (con alta expresión del ligando 1 de muerte programada [PD-L1]), que progresó a pesar de administrar múltiples de líneas quimioterapia y posteriormente remitió de manera espontánea. Presentación del caso: La paciente presentaba hemoptisis y se le diagnosticó CPNM poco diferenciado en estadio IIIA mediante biopsia broncoscópica. No había características notables en su historial médico y su estado funcional era moderado. El plan inicial de tratamiento consistió en cirugía después de quimioterapia neoadyuvante. A pesar de la quimioterapia convencional, la tomografía computada (TC) de seguimiento mostró una progresión gradual del tumor, y la paciente decidió no continuar con el tratamiento después de la quimioterapia de quinta línea. Sin embargo, el tamaño de la masa tumoral disminuyó marcadamente en una TC torácica de seguimiento un año después de suspender la quimioterapia. Asimismo, imágenes de tomografía por emisión de positrones tomadas en el seguimiento mostraron una menor actividad metabólica en la masa tumoral, y una muestra de biopsia percutánea de la masa pulmonar reducida no reveló células tumorales viables. Se confirmó el diagnóstico de RE de CPNM, y la paciente no mostró progresión tumoral en el seguimiento, nueve meses después. Más tarde, la inmunotinción para PD-L1 mostró una alta positividad (>99%) en las células tumorales iniciales. Conclusión: Nuestro caso, que muestra la RE de CPNM avanzado, poco diferenciado y refractario a múltiples líneas de quimioterapia, sugiere una asociación entre la inmunidad y la regresión tumoral.

Background Spontaneous remission (SR) of cancer is a very rare phenomenon of unknown mechanism. In particular, SR of non-small cell lung cancer (NSCLC) has been scarcely reported. We present the case of a 74-year-old woman with advanced, poorly differentiated NSCLC (highly expressing programmed death ligand-1 [PD-L1]) that progressed despite multiple lines of chemotherapy but then spontaneously remitted. CASE presentation The patient presented with hemoptysis and was diagnosed with stage IIIA poorly differentiated NSCLC via bronchoscopic biopsy. She had an unremarkable medical history and moderate performance status. The initial treatment plan was surgery after neoadjuvant chemotherapy. Despite conventional chemotherapy, follow-up chest computed tomography (CT) showed gradual tumor progression and she decided against further treatment after fifth-line chemotherapy. However, the size of lung mass was markedly decreased on follow-up chest CT one year after ceasing chemotherapy. Also, follow-up positron emission tomography images showed decreased metabolic activity in the lung mass and a percutaneous biopsy specimen from the diminished lung mass revealed no viable tumor cells. A diagnosis of SR of NSCLC was confirmed, and the patient was without tumor progression on follow-up nine months later. Later, PD-L1 immunostaining revealed high positivity (> 99%) in initial tumor cells. Conclusion Our case showing SR of poorly advanced NSCLC refractory to multiple lines of chemotherapy suggested the association between immunity and tumor regression.

Background Circulating tumor DNA (ctDNA) is cell-free DNA that is released into peripheral blood by tumor cells. ctDNA harbors somatic mutations and mutant ctDNA obtained from blood can be used as a biomarker in advanced non-small cell lung cancer (NSCLC). In this study, we investigated the clinicopathological properties of tumors that shed ctDNA in surgically resected NSCLC patients. Methods Consecutive cases of NSCLC with matching surgically resected tissue specimens and peripheral or specimen blood samples were eligible for this study. EGFR and KRAS mutations in plasma ctDNA and formalin-fixed paraffin-embedded tissue were analyzed using peptide nucleic acid clamping-assisted method. The plasma and tissue results were compared according to clinicopathological features. Results Mutation analyses were available for 36 cases. EGFR and KRAS mutations were present in 41.7% (15/36) and 16.7% (6/36) of tissue samples, respectively. Among EGFR and KRAS-mutant tumors, plasma mutation detection sensitivity was 13.3% (2/15) for EGFR and 33.3% (2/6) for KRAS. The presence of ctDNA in plasma was significantly associated with higher pathological tumor stage (p = 0.028), nodal metastasis (p = 0.016), solid adenocarcinoma pattern (p = 0.003), tumor necrosis (p = 0.012), larger primary tumor diameter (p = 0.002) or volume (p = 0.002), and frequent mitosis (p = 0.018) in tissue specimens. All tumors larger than 4 cm in maximal diameter or 25 cm3 in volume shed ctDNA in plasma. In subgroup analysis among EGFR mutated adenocarcinoma, ctDNA was significantly associated with nodal metastasis (p = 0.029), vascular invasion (p = 0.029), solid adenocarcinoma pattern (p = 0.010), and tumor necrosis (p = 0.010), high mitotic rate (p = 0.009), large pathological tumor size (p = 0.027), and large tumor volume on CT (p = 0.027). Conclusion We suggest that primary or total tumor burden, solid adenocarcinoma morphology, tumor necrosis, and frequent mitosis could predict ctDNA shedding in pulmonary adenocarcinoma.

BACKGROUND Rapidly progressive pneumoconiosis (RPP) occasionally occurs in coal workers, particularly those with high exposure to silica. Here, we report the case of a 64-year-old male miller with RPP. CASE SUMMARY The patient had a persistent cough for one month and had been clinically diagnosed with pulmonary tuberculosis in 2011. He worked in a stone processing factory from the ages of 20 through 37 and has owned his own mill for the past 25 years. His chest radiograph showed significant increases in the size and number of lung nodules since his last follow-up in 2013. By percutaneous needle lung biopsy, the nodular lesions showed diffuse infiltration of phagocytic macrophages and birefringent crystals by polarizing microscopy. He was finally diagnosed with RPP of mixed dust pneumoconiosis combined with silicosis. CONCLUSION In this case, mixed dust pneumoconiosis with silicosis might be accelerated by persistent exposure to grain dust from working in a mill environment.

Background: Lung cancer is being increasingly detected in the early stages, highlighting the importance of lung cancer screening. However, there is no consensus on the post-operative management of stage IB non-small cell lung cancer (NSCLC). Therefore, this study aimed to identify the predictive factors for prognosis of stage IB NSCLC and determine the efficacy of adjuvant chemotherapy on recurrence and survival. Methods: We enrolled 89 patients with stage IB NSCLC who underwent complete resection surgery at Gangnam Severance Hospital from Jan 2008 to Dec 2014. As per the National Comprehensive Cancer Network guidelines, patients were considered to be at high risk when they showed poorly differentiated tumors, lymphovascular invasion, tumor size >4 cm, and visceral pleural invasion (VPI). Results: Among the 89 patients, 27 underwent adjuvant chemotherapy. Young patients or patients with squamous cell lung cancer received adjuvant chemotherapy frequently. Adjuvant chemotherapy was not a significant factor for disease-free survival and overall survival. Adjuvant chemotherapy did not show a significant protective effect for survival, even for high-risk patients. However, VPI was a significant risk factor for disease-free survival [hazard ratio (HR): 7.051; 95% confidence interval (CI): 1.570–31.659; P=0.011] and overall survival (HR: 8.289; 95% CI: 1.036–66.307; P=0.046), even after adjustment for various factors. Conclusions: Adjuvant chemotherapy does not affect the prognosis of stage IB NSCLC, even in high-risk patients. Additionally, VPI is a strong prognostic factor of stage IB NSCLC.

BACKGROUND. NUT carcinoma is a rare aggressive disease caused by BRD4/3‐NUT fusion, and C‐MYC upregulation plays a key role in the pathogenesis. Here, we report on the clinicopathological characteristics of Korean patients with NUT carcinoma and the in vitro efficacy of MYC‐targeting agents against patient‐derived NUT carcinoma cell lines. MATERIALS AND METHODS. Thirteen patients with NUT carcinoma were evaluated for p53, C‐MYC, epidermal growth factor receptor (EGFR), HER2, and programmed cell death ligand 1 (PD‐L1) by immunohistochemistry. The half maximal inhibitory concentration (IC(50)) values of NUT carcinoma cell lines (SNU‐2972‐1, SNU‐3178S, HCC2429, and Ty‐82) were determined using MYC‐targeting agents, including bromodomain and extraterminal (BET) inhibitors (I‐BET, OTX‐015, AZD5153) and histone deacetylase (HDAC) inhibitors (vorinostat, romidepsin, panobinostat, CUDC‐907). RESULTS. Primary tumor sites included head and neck (n = 9) and lung (n = 4). The patient age ranged from 8 to 73 years with the male/female ratio of 1.2:1. Nine patients died at 3–23.6 months (median, 10.6) after diagnosis. Eight patients had been misdiagnosed initially with other diseases. One patient with metastatic NUT carcinoma who received mass excision plus metastasectomy followed by chemoradiotherapy was a long‐term survivor (>27 months). Although expressions of C‐MYC (8/12, 73%) and p53 (12/12, 100%) were commonly observed, EGFR, HER2, and PD‐L1 expressions were observed in 2 of 7 (29%), 2 of 8 (25%), and 1 of 12 (8.3%) patients, respectively. BET and HDAC inhibitors showed variable but limited in vitro efficacy. However, a dual HDAC/PI3K inhibitor, CUDC‐907, was most potent against NUT carcinoma cells, with an IC(50) of 5.5–9.0 pmol/L. Consistent with these findings, kinome short interfering RNA screening showed a positive hit for PI3KCA in NUT carcinoma cells. Panobinostat (IC(50), 0.4–1.3 nmol/L) and a bivalent BET inhibitor, AZD5153 (IC(50), 3.7–8.2 nmol/L), also showed remarkable efficacies. CONCLUSION. East Asian patients with NUT carcinoma showed dismal survival outcomes like Western patients, and CUDC‐907 might be promising in NUT carcinoma treatment. IMPLICATIONS FOR PRACTICE. NUT carcinoma (NC) is a disease caused by BRD‐NUT fusion leading to C‐MYC upregulation. NC is often misdiagnosed and very aggressive, requiring development of effective therapeutic strategy. This article presents the clinicopathological features of the largest series of NCs in East Asians and preclinical sensitivities to MYC‐targeting agents in NC cell lines. Patients with NC had grave outcomes and poor response to treatment. Among MYC‐targeting agents, including BET and HDAC inhibitors, CUDC‐907 (a dual PI3K/HDAC inhibitor) was most effective against NC cells, followed by panobinostat (an HDAC inhibitor) and AZD5153 (a bivalent BET inhibitor). CUDC‐907 might be promising in NC treatment.

The authors compared maximal tumor diameters between fresh lung tissue and axial and multiplanar reformatted chest computed-tomography (CT) images in lung adenocarcinoma and investigated the factors affecting tumor-size discrepancies. This study included 135 surgically resected lung adenocarcinomas. An experienced pulmonary pathologist aimed to cut the largest tumor section and measured pathological tumor size (PTS) in fresh specimens. Radiological maximal tumor sizes (RTS) were retrospectively measured on axial (RTSax) and multiplanar reformatted (RTSre) chest CT images. Mean PTS, RTSax, and RTSre were 19.13 mm, 18.63 mm, and 20.80 mm, respectively. RTSre was significantly larger than PTS (mean difference, 1.68 mm; p

Cryptococcus neoformans는 주로 면역이 저하된 환자에서 기회 감염을 일으키는 진균이다. 그러나 면역이 정상인 환자에서도 다양한 감염을 일으킬 수 있다. 림프절을 침범한 폐 크립토코쿠스증은 정상 면역을 가진 사람에서는 상대적으로 드물게 발생한다. 고열과 지속적인 기침을 주소로 병원에 온 17세 여자 청소년이 가슴X선 영상검사 및 컴퓨터단층촬영에서 전방 종격동에서 우측 쇄골하 부위까지 침범된 종괴를 보여 초음파 유도하 총생검 검사로 크립토코쿠스증을 진단하였다. 각종 면역 검사에서는 이상 소견이 발견되지 않았다. 환자는 2주간 암포테리신 B와 플루시토신으로 치료 후 8개월간 플루코나졸로 치료하였고 완쾌되었다. 본 증례를 통해 크립토코쿠스증의 특징을 이해하고 정상 면역 환자에게서도 크립토코쿠스증이 발생할 수 있음을 염두에 두고 진단을 내리는 것이 바람직하겠다.

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Background We aimed to identify clinicopathologic characteristics and risk of invasiveness of lung adenocarcinoma in surgically resected pure ground-glass opacity lung nodules (GGNs) smaller than 2 cm. Methods Among 755 operations for lung cancer or tumors suspicious for lung cancer performed from 2012 to 2016, we retrospectively analyzed 44 surgically resected pure GGNs smaller than 2 cm in diameter on computed tomography (CT). Results The study group was composed of 36 patients including 11 men and 25 women with a median age of 59.5 years (range, 34–77). Median follow-up duration of pure GGNs was 6 months (range, 0–63). Median maximum diameter of pure GGNs was 8.5 mm (range, 4–19). Pure GGNs were resected by wedge resection, segmentectomy, or lobectomy in 27 (61.4%), 10 (22.7%), and 7 (15.9%) cases, respectively. Pathologic diagnosis was atypical adenomatous hyperplasia, adenocarcinoma in situ, minimally invasive adenocarcinoma (MIA), or invasive adenocarcinoma (IA) in 1 (2.3%), 18 (40.9%), 15 (34.1%), and 10 (22.7%) cases, respectively. The optimal cutoff value for CT-maximal diameter to predict MIA or IA was 9.1 mm. In multivariate analyses, maximal CT-maximal diameter of GGNs ≥10 mm (odds ratio, 24.050; 95% confidence interval, 2.6–221.908; p = 0.005) emerged as significant independent predictor for either MIA or IA. Estimated risks of MIA or IA were 37.2, 59.3, 78.2, and 89.8% at maximal GGN diameters of 5, 10, 15, and 20 mm, respectively. Conclusion Pure GGNs were highly associated with lung adenocarcinoma in surgically resected cases, while estimated risk of GGNs invasiveness gradually increased as maximal diameter increased.

Sclerosing pneumocytoma (SP) of the lung is a rare benign neoplasm. Here, we describe an unusual presentation of SP with a wax-and-wane pattern of growth in a 47-year-old woman. Tumor diameter decreased over a 3-year follow-up period and then increased on serial follow-up computed tomography scans. The mass showed high signal intensity on both T1- and T2-weighted chest magnetic resonance imaging (MRI) and early enhancement with a plateau on dynamic MRI. We speculate that intratumoral bleeding and resorption processes accounted for the changes in tumor size.

The gene deleted in malignant brain tumor 1 (DMBT1) encoding a large scavenger receptor cysteine-rich protein was originally identified based on its deletion in a brain tumor cell line. The DMBT1 protein is involved in mucosal immune defense, epithelial differentiation and tumor suppression. In the present study, the clinicopathologic significance of DMBT1 protein expression in stool and tissue samples of colorectal cancer (CRC) patients was evaluated. Western blot analysis of fecal DMBT1 was performed for patients with CRC (n=177), colorectal adenoma (n=61), inflammatory bowel diseases (IBDs; n=54) and healthy individuals as the control group (n=151). Immunohistochemical analysis of tissue expression of DMBT1 was performed in 385 primary CRC tissues. Fecal DMBT1 expression was higher in CRC and IBD patients than in healthy controls or adenoma patients (P

Cancer is the leading cause of death in the Republic of Korea and cancer death accounts for 27.8% of the total deaths, which is not only a social issue but also a concern for the public. Among the cancer death rates, lung cancer mortality account for 34 deaths per 100,000 populations, making it the number one cancer death rate. In a preliminary report on cancer death in 2012, the lung cancer mortality ratio showed the regional variation indicating that there were differences in the qualitative level and the structure among the medical care benefit agency and in the assessment of the treatment process. Therefore, the Health Insurance Review and Assessment Service (HIRA) had begun evaluation of the assessment of lung cancer treatment since 2014 to improve the quality of lung cancer care through evaluation and feeds back the results of lung cancer care process. In this report, authors described the current Indicators for the lung cancer adequacy assessment proposed by HIRA and results of the evaluation reported in 2017.

A reliable, non-invasive diagnostic method is needed for early detection and serial monitoring of cardiotoxicity, a well-known side effect of chemotherapy. This study aimed to assess the feasibility of T1-mapping cardiac magnetic resonance imaging (CMR) for evaluating subclinical myocardial changes in a doxorubicin-induced cardiotoxicity rabbit model. Adult male New Zealand White rabbits were injected twice-weekly with doxorubicin and subjected to CMR on a clinical 3T MR system before and every 2–4 weeks post-drug administration. Native T1 and extracellular volume (ECV) values were measured at six mid-left ventricle (LV) and specific LV lesions. Histological assessments evaluated myocardial injury and fibrosis. Three pre-model and 11 post-model animals were included. Myocardial injury was observed from 3 weeks. Mean LV myocardium ECV values increased significantly from week 3 before LV ejection fraction decreases (week 6), and ECVs of the RV upper/lower insertion sites and papillary muscle exceeded those of the LV. The mean native T1 value in the mid-LV increased significantly increased from week 6, and LV myocardium ECV correlated strongly with the degree of fibrosis (r = 0.979, p

Aim Formalin fixation can cause tumor shrinkage. We prospectively evaluated the effect of overnight formalin fixation on tumor size and the effect of clinicopathological parameters on changes in tumor size in small-sized non-small cell lung cancer (NSCLC). Methods and results Our study included 126 surgically resected NSCLC specimens submitted in a fresh state. We measured the largest cross-sectional tumor diameters in the fresh and formalin-fixed specimens. Tumor size significantly differed (mean, 0.066 cm; p 10% change in tumor size after formalin fixation was increased in tumors with lepidic pattern (odds ratio [OR], 6.268; p=0.001), in subsolid tumors (OR, 4.068; p=0.011), and in adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA) histology (OR, 6.545; p=0.003). Pleural dimpling lowered the risk for tumor size change after fixation (OR, 0.162; p=0.019). On multivariate analysis, a lepidic pattern (OR, 4.601; p=0.010) and AIS/MIA histology (OR, 4.381; p=0.026) were still significant risk factors. Longer ischemic time was the single risk factor for tumor shrinkage in the invasive adenocarcinoma subgroup (OR, 5.357; p=0.021). Conclusion NSCLC tumors shrank or enlarged by 4.06% after overnight formalin fixation. A lepidic pattern and AIS/MIA histology were independent risk factors for both significant tumor shrinkage and growth after fixation. Longer ischemic time was the single risk factor for significant tumor shrinkage in invasive adenocarcinoma. This article is protected by copyright. All rights reserved.

Endoscopic ultrasound (EUS) fine needle aspiration (FNA) biopsy is commonly used in the diagnosis of pancreatic tumors. Although adenocarcinoma is the most commonly diagnosed primary pancreatic neoplasm, other neoplasms can also arise in this organ. For accurate diagnosis, pathologists must be familiar with the cytomorphology associated with all types of pancreatic tumors. Serous cystadenoma (SCA) is a rare, benign neoplasm that originates in the centro-acinar epithelium of the pancreas. Excluding any symptomatic or diagnostic uncertainty, patients presenting with SCA need no further management. Here, we report a case of pancreatic SCA that was suspected to be adenocarcinoma in preoperative test using EUS-guided FNA.

Epidermal growth factor receptor (EGFR) is frequently overexpressed in triple-negative breast cancer and is emerging as a therapeutic target. EGFR gene copy number alteration and mutation are highly variable and scientists have been challenged to define their prognostic significance in triple-negative breast cancer. We examined EGFR protein expression, EGFR gene copy number alteration and mutation of exon 18 to 21 in 151 cases of triple-negative breast cancer and correlated these findings with clinical outcomes. In addition, intratumoral agreement of EGFR protein overexpression and gene copy number alteration was evaluated. EGFR overexpression was found in 97 of 151 cases (64%) and high EGFR gene copy number was detected in 50 cases (33%), including 3 gene amplification (2%) and 47 high polysomy (31%). Five EGFR mutations were detected in 4 of 151 cases (3%) and included G719A in exon 18 (n=1), V786M in exon 20 (n=1), and L858R in exon 21 (n=3). One case had two mutations (G719A and L858R). High EGFR copy number, but not EGFR mutation, correlated with EGFR protein overexpression. Intratumoral heterogeneity of EGFR protein overexpression and EGFR copy number alteration was not significant. In survival analyses, high EGFR copy number was found to be an independent prognostic factor for poor disease-free survival in patients with triple-negative breast cancer. Our findings showed that EGFR mutation was a rare event, but high EGFR copy number was relatively frequent and correlated with EGFR overexpression in triple-negative breast cancer. Moreover, high EGFR copy number was associated with poor clinical outcome in triple-negative breast cancer, suggesting that evaluation of EGFR copy number may be useful for predicting outcomes in patients with triple-negative breast cancer and for selecting patients for anti-EGFR-targeted therapy.

Metastatic carcinoma that causes appendicitis is extremely rare. To our knowledge, metastatic cholangiocarcinoma in the appendix has been reported in only 1 case in the English literature. We report herein the case of an 87-year-old woman who presented with abdominal pain and jaundice. Advanced cholangiocellular carcinoma and a proximal appendiceal mass with appendicitis were detected on contrast-enhanced computed tomography and positron emission tomography/computed tomography. After elective laparoscopic appendectomy and wedge resection of the cecum, pathologic results revealed metastatic adenocarcinoma from extrahepatic cholangiocellular carcinoma in the appendix.

Introduction:We aimed to evaluate the correlation between the size of the solid component on thin-section computed tomography (CT) and invasive component on pathology in small lung adenocarcinomas manifesting as subsolid nodules.Methods:Fifty-nine subsolid nodules in 58 patients were evaluated. The maximum diameters of subsolid nodules and the solid component on CT were measured by two radiologists in three-dimensional (3D) and two-dimensional (2D) planes using in-house software. In addition, the maximum diameters of the tumor and invasive component were measured on pathology by two pathologists. CT measurements were compared with pathologic measurements.Results:There was a strong correlation between the size of the solid component on CT and invasive component on pathology, as well as the size of subsolid nodules and the tumor size (r = 0.82–0.87 for 3D measurement, 0.72–0.88 for 2D measurement; p < 0.0001). The size of subsolid nodules in 3D and 2D measurements was significantly larger than tumor size (p < 0.0001). In regard to measurement of the solid component, 3D measurements tended to be larger than the size of the invasive component whereas 2D measurement tended to be similar to the size of the invasive component. By applying a size criteria of solid component that was 3 mm or lesser in maximum diameter, preinvasive and minimally invasive adenocarcinoma was predicted with a specificity of 100% (28 of 28).Conclusion:We found a significant correlation between the size of the solid component on thin-section CT and the invasive component on pathology.

Background Pulmonary sclerosing hemangioma (PSH) has been reported to show increased FDG uptake and be potential false-positives on 18F-FDG PET/CT examination. However, it is still unclear whether the previously-reported high FDG uptake is a universal characteristic of PSH, and furthermore, there have been no investigations on what kind of radiologic or histologic features may have been related with its FDG uptake values. Purpose To investigate the 18F-FDG PET/CT features of pulmonary sclerosing hemangiomas (PSHs), and to evaluate the relating factors with their FDG uptake values. Material and Methods We identified 10 PSHs in eight patients who had a pathologic diagnosis and available antecedent 18F-FDG PET/CT images. 18F-FDG PET/CT images were investigated both qualitatively and quantitatively, along with their histopathologic features. Correlation between 18F-FDG PET features and radiologic as well as histopathologic features were also evaluated. Results Mean diameter of the 10 PSHs in our study was 16.9 mm ± 6.26 (range 5-25 mm). Four tumors showed intense uptake, and four tumors showed moderate uptake on 18F-FDG PET/CT scans. In the remaining two tumors, there were no significant FDG uptakes. The SUVmax of tumors ranged from 0.60-4.7 (median 2.30; 2.51 ± 1.42), and was significantly correlated with the tumor size (r = 0.754, P = 0.012) and three out of four tumors ≥2 cm (75%) showed intense FDG uptake and their SUVmax values were greater than 2.5. Immunohistochemical results for GLUT-1, GLUT-4, and Ki-67 and other pathologic features were not correlated with the tumors’ FDG uptake. Conclusion The majority of PSHs show increased FDG uptakes, and their SUVmax values are significantly correlated with their tumor size. PSH ≥2 cm can frequently be falsely interpreted as malignancy in FDG-PET/CT. Further studies with large study population are warranted to confirm our observations.

Compound EGFR mutations, defined as double or multiple mutations in the EGFR tyrosine kinase domain, are frequently detected with advances in sequencing technology but its clinical significance is unclear. This study analyzed 61 cases of EGFR mutation positive lung adenocarcinoma using next-generation sequencing (NGS) based repeated deep sequencing panel of 16 genes that contain actionable mutations and investigated clinical implication of compound EGFR mutations. Compound EGFR mutation was detected in 15 (24.6%) of 61 cases of EGFR mutation-positive lung adenocarcinoma. The majority (12/15) of compound mutations are combination of the atypical mutation and typical mutations such as exon19 deletion, L858R or G719X substitutions, or exon 20 insertion whereas 3 were combinations of rare atypical mutations. The patients with compound mutation showed shorter overall survival than those with simple mutations (83.7 vs. 72.8 mo; P = 0.020, Breslow test). Among the 115 missense mutations discovered in the tested genes, a few number of actionable mutations were detected irrelevant to the subtype of EGFR mutations, including ALK rearrangement, BCL2L11 intron 2 deletion, KRAS c.35G>A, PIK3CA c.1633G>A which are possible target of crizotinib, BH3 mimetics, MEK inhibitors, and PI3K-tyrosine kinase inhibitors, respectively. 31 missense mutations were detected in the cases with simple mutations whereas 84 in those with compound mutation, showing that the cases with compound missense mutation have higher burden of missense mutations (P = 0.001, independent sample t-test). Compound EGFR mutations are detected at a high frequency using NGS-based repeated deep sequencing. Because patients with compound EGFR mutations showed poor clinical outcomes, they should be closely monitored during follow-up.

A 39-year-old woman visited an outpatient clinic complaining of nausea and vomiting for 1 week. She had been experiencing dyspepsia for several months. Her endoscopic gastroduodenography did not show any remarkable findings. She was lean and of short stature, with a weight of 29 kg, height of 147 cm, and an approximated body mass index of 13.49 kg/m2. She had some hearing difficulties and cognitive dysfunction. Her parents died when she was a teenager; her mother passed away because of diabetic complications in her third decade. She was a nonsmoker and denied any history of hypertension or symptoms of chest pain except for alleged diabetes mellitus. Her chest x-ray film showed cardiomegaly, and ECG revealed normal sinus rhythm and left ventricular hypertrophy with T-wave inversion along V4≈6 precordial lead. Her blood troponin-T and creatine kinase MB levels were mildly elevated. Lactate dehydrogenase and B-type natriuretic peptide levels were also elevated to 456 IU/L and 147.0 pg/mL, respectively. Her hemoglobin A1C level was elevated, whereas Islet cell antibody and insulin antibody levels were normal, suggesting type 2 diabetes mellitus. On pure tone audiometry, sensory neural hearing loss at …

Purpose: NUT midline carcinoma (NMC) is an aggressive and poorly differentiated carcinoma defined by chromosomal rearrangements of NUT gene, which is fused to the BET family genes (BRD3/4). Although NMC is extremely rare and mostly reported in a Western population, clinico-pathologic findings of Asian NMC patients are not well studied. Here, we performed the clinicopathologic analysis of Korean NMC cases and in vitro efficacy of MYC-targeting agents against patient-derived NMC cell lines. Experimental Design: A total of 12 NMC patients (3 thoracic and 9 head and neck origins) were collected in Korean multi-centers by immunohistochemistry (IHC) and fluorescence in situ hybridization for NUT. IHC staining was performed for c-MYC, p53, EGFR, HER2, and PD-L1. NMC cell lines (SNU-2972-1, SNU-3178S, HCC2429, and Ty-82) were exposed to MYC-targeting agents including BET (I-BET, OTX-015, and AZD5153) and HDAC (vorinostat, romidepsin, panobinostat, and CUDC-907) inhibitors. Cell viability assays were performed and IC50 values were determined. Results: Primary sites of tumor included sinonasal area (n=7), salivary gland (n=2), and thorax/lung (n=3). The median age was 47.5 years (range, 8-73 years) with equal male-to-female ratio. NUT immunostaining showed diffuse positivity in all except for one who had focal NUT positivity. C-MYC and p53 were expressed in all evaluated cases. PD-L1 expression was observed only in a patient (8.3%). Seven of 12 patients died at 3-24 months (median, 9 months) after diagnosis. Long-term survivor was observed in one patient with stage IV NMC who received mass excision plus metastasectomy followed by 6 cycles of docetaxel plus cisplatin and radiotherapy (survival > 27 months). Although BET and HDAC inhibitors showed limited in vitro efficacies against NMC cells, a dual HDAC/PI3K inhibitor, CDUC-907 exhibited the most potent efficacy with the IC50 of 6.2 to 9 pmol/L. Conclusions: Korean NMC patients pursued grave prognosis like Western patients except one long-term survivor who received tri-modality treatments. Dual HDAC/PI3K inhibitor might be promising in NMC treatment. Citation Format: Soyeon Kim, Minsun Jung, Heae Surng Park, Sun Och Yoon, Soon Won Hong, Weon-Seo Park, Bhumsuk Keam, Hyun Jik Kim, Dong-Wan Kim, Young Tae Kim, Dae Seong Heo, Tae Min Kim, Yoon Kyung Jeon. Clinicopathologic findings and in vitro efficacy of MYC-targeting agentsin NUT midline carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3990.

Background Biopsy for lung cancer diagnosis is usually done at a single site. But it is unclear that genetic information at one biopsy site represents that of other lesions and is sufficient for therapeutic decision making. Methods Non-synonymous mutations and insertions/deletions of 16 genes containing actionable mutations, and intron 2 deletion polymorphism of Bcl2-like11 were analyzed in 41 primary tumor and metastatic lymph node (L/N) matched, pStage IIA ~ IIIA non-small cell lung cancer (NSCLC) samples using a next generation sequencing based technique. Results A total of 249 mutations, including 213 non-synonymous mutations, 32 deletions, and four insertions were discovered. There was a higher chance of discovering non-synonymous mutations in the primary tumors than in the metastatic L/N (138 (64.8%) vs. 75 (35.2%)). In the primary tumors, 106 G > A:C > T transitions (76.8%) of 138 non-synonymous mutations were detected, whereas in the metastatic L/N, 44 (58.7%) of 75 were discovered. A total 24 (11.3%) out of 213 non-synonymous mutations were developed in the context of APOBEC signature. Of those, 21 (87.5%) was detected in the primary tumors and 4 (16.7%) was detected in the metastatic L/N. When the mutation profiles between primary tumor and metastatic L/N were compared, 13 (31.7%) of 41 cases showed discrepant mutation profile. There were no statistically significant differences in disease free survival and overall survival between groups showing identical mutation profiles and those with discrepancy between primary and metastatic L/N. Conclusions Genetic heterogeneity between the primary and L/N metastatic lesions is not infrequent finding to consider when interpreting genomic data based on the result of one site inspection. A large prospective study may be needed to evaluate the impact of genetic heterogeneity on the clinical outcomes of NSCLC patients. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2049-z) contains supplementary material, which is available to authorized users.

This study aimed to identify the impact of preoperative colonoscopic tattooing (PCT) on lymph node harvest in T1 colorectal cancer patients. One hundred and forty-three patients were included who underwent curative resection and were diagnosed with T1 colorectal cancer. These patients were categorized into the tattooing group and the non-tattooing group depending on whether preoperative India ink tattooing was done. Clinicopathological findings and lymph node harvest were compared between the two groups. The median number of lymph nodes examined was 18 in the tattooing group and 13 in the non-tattooing group (p

Endobronchial metastasis is defined by bronchoscopically visible extrapulmonary tumors with lesions histologically identical to the primary tumors. Carcinomas of the breast, kidney, and colorectum are the most commonly encountered solid tumors causing endobronchial metastases [1], whereas such metastases arising from the tumors of uterine cervix are relatively rare. While there have been many case reports on endobronchial metastasis of uterine cervical squamous cell carcinoma, there is only one reported case of metastatic endobronchial adenocarcinoma from the uterine cervix [2] and this report focused only on endoscopic treatment. Herein, we report a case of metastatic endobronchial adenocarcinoma from the uterine cervix with discuss on the differential diagnosis.

Rhabdomyomatous mesenchymal hamartoma is a rare congenital tumor and usually occurring in the head and neck. Characteristically, this tumor is composed of various mesenchymal elements such as adipose tissue, blood vessels, collagen fibers, elastic fibers, and peripheral nerves in random orientation. We present a 7-year-old boy with an intranasal mass developed after the trauma and who had a diagnosis of rhabdomyomatous mesenchymal hamartoma.

Intraosseous hemangioma is a benign vascular tumor of the bone. The most common site of this tumor is the vertebral body, followed by calvarial bones. Intraosseous hemangioma of the nasal cavity is extremely rare. This lesion had en bloc been resected through the endoscopic approach without preoperative embolization, significant intraoperative bleeding, and postoperative events. We report a rare case of intraosseous hemangioma of the nasal cavity with distinctive radiologic findings. Clinicians should be well familiar with the radiologic findings and clinical features of this tumor, which would be helpful in making a correct diagnosis and management plan.

Fluorescence in situ hybridization (FISH) is currently used to detect non-small cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase (ALK) gene rearrangement, who are candidates for ALK inhibitor therapy. However, FISH may not be a practical method for screening for ALK-positive patients in a large population due to its cost and difficulty in interpretation. We investigated the role of immunohistochemistry (IHC) to screen for ALK rearrangement in advanced NSCLC. We identified 1,166 stage IIIB or IV NSCLC patients with non-squamous histology from the Seoul National University Hospital NSCLC database. To enrich ALK-positive cases, we selected 262 patients who were either EGFR wild-type or non-responders to previous EGFR tyrosine kinase inhibitors (TKI). ALK IHC and ALK FISH were performed on formalin-fixed, paraffin-embedded tissue. ALK protein was expressed in 28 (10.7%) tumors in 262 patients. ALK FISH was positive in 25 (9.5%) cases. All patients with IHC score of 3 (n=9) were FISH-positive and all patients with score of 0 (n=234) were FISH-negative. Among patients with IHC scores of 1 and 2, five (83.3%, 5/6) and eleven (84.6%, 11/13) were FISH-positive, respectively. The sensitivity and specificity of ALK IHC with intensity score of 1 or more were 100% and 98.7%, respectively. IHC can be a useful test for screening ALK FISH-positive cases in advanced NSCLC. FISH testing should be considered for advanced NSCLC patients with tumors showing mild to moderate staining for ALK by IHC to confirm ALK translocation.

The purpose of this study was to investigate the overall survival (OS) of patients with advanced ALK-positive nonsmall cell lung cancer (NSCLC) who were managed in the pre-ALK inhibitor era and to compare their survival with that of a matched case cohort of ALK wild-type (WT) patients.Data from 1166 patients who had stage IIIB/IV NSCLC with nonsquamous histology were collected from the NSCLC database of Seoul National University Hospital between 2003 and 2009. ALK fluorescence in situ hybridization (FISH) was used to analyze 262 patients who either had the WT epidermal growth factor receptor (EGFR) or were nonresponders to previous EGFR tyrosine kinase inhibitor (TKI) therapy. Overall survival (OS) was compared between 3 groups: 1) ALK-positive patients, 2) EGFR mutation-positive patients, and 3) ALK-WT/EGFR-WT patients. Progression-free survival (PFS) after first-line chemotherapy and EGFR TKIs also was analyzed.Twenty-three patients were ALK-positive according to FISH analysis and did not receive ALK inhibitors during follow-up. The median OS for ALK-positive patients, EGFR mutation-positive patients, and WT/WT patients was 12.2 months, 29.6 months, and 19.3 months, respectively (vs EGFR mutation-positive patients, P = .001; vs WT/WT, P = .127). The PFS after first-line chemotherapy for the 3 groups was not different. However, the PFS for patients who received EGFR TKIs was shorter in ALK-positive patients compared with the other 2 groups (vs EGFR mutation-positive patients, P.001; vs WT/WT, P.021).In the pre-ALK inhibitor era, ALK-positive patients experienced the shortest survival, although it did not differ statistically from that of WT/WT patients. Although their responses to platinum-based chemotherapy were not different from comparator groups, ALK-positive patients were even more resistant to EGFR TKI treatment than WT/WT patients.

The purpose of this study was to investigate the long-term clinical course of non-specific interstitial pneumonia (NSIP) and to determine which factors are associated with a response to steroid therapy and relapse. Thirty-five patients with pathologically proven NSIP were included. Clinical, radiological, and laboratory data were reviewed retrospectively. The male-to-female ratio was 7:28 (median age, 52 yr). Thirty (86%) patients responded to steroid therapy, and the median follow-up was 55.2 months (range, 15.9-102.0 months). Five patients (14%) showed sustained disease progression and three died despite treatment. In the five with sustained disease progression, NSIP was associated with various systemic conditions, and the seropositivity of fluorescent antinuclear antibody was significantly associated with a poor response to steroids (P = 0.028). The rate of relapse was 25%, but all relapsed patients improved after re-treatment. The initial dose of steroids was significantly low in the relapse group (P = 0.020). In conclusion, progression is associated with various systemic conditions in patients who show progression. A low dose of initial steroids is significantly associated with relapse.

Cystic renal cell carcinoma has more favorable biology than noncystic renal cell carcinoma. Recently cystic change detected grossly or by low power microscopy was found to be a good prognostic factor for clear cell renal cell carcinoma. We assessed the optimal cutoff value of the proportion of cystic change with prognostic significance for clear cell renal cell carcinoma.We identified 223 patients with clear cell renal cell carcinoma who underwent partial or radical nephrectomy between 2001 and 2003. The cystic proportion of the tumor cut surface was calculated objectively and its prognostic significance was evaluated.The ROC curve showed that a cystic percent of between 6% and 10% was appropriate to detect patients with renal cell carcinoma at low risk for cancer mortality and progression. A cutoff of 6% was adopted as a break point of cystic change for patient stratification. We analyzed the records of 87 patients (39.0%) with tumors with a cystic proportion of greater than 5%, that is 6% or greater. They had significantly lower stage and lower Fuhrman nuclear grade than patients with tumors with a cystic change of 5% or less (each p0.0001). On multivariate analysis a cystic proportion of more than 5% was a good prognostic indicator of cancer specific and progression-free survival (HR 0.221, p=0.044 and HR 0.214, p=0.004, respectively).In patients with clear cell renal cell carcinoma a cystic change comprising more than 5% of the tumor is a good independent predictor of survival.